Postmenopausal (estrogen deficiency-induced) osteoporosis is a major public health problem predisposing to fracture and resulting in significant morbidity and mortality. Current therapies can stabilize bone mass but can not repair or restore lost bone. Thus, a critical need exists to improve therapeutics for the treatment of osteoporosis. Growth factors are essential for hone repair, and exogenous growth factors can augment bone formation. We have demonstrated that the combination of platelet- derived growth factor (pDGF) and insulin-like growth factor-I (IGF-I) can dramatically stimulate bone repair when applied locally in vivo. However, the systemic administration of growth factors to stimulate generalized bone growth is limited by their equally potent, and less desirable, extra- skeletal actions. This proposal will examine whether IGF-I and PDGF, linked to a bone seeking agent which targets them to bone and renders them inactive in the circulation, will prevent bone loss or restore bone mass in estrogen deficient rats. The effects of the growth factors on bone will be followed using biochemical markers of bone metabolism, state-of-the-art non-invasive bone densitometry, histomorphometry and mechanical strength testing. These studies are designed to lead directly to further investigations to develop clinically useful therapeutic agents for osteoporosis.